Our
Science
Our Approach
The Pan-PPAR Advantage
PPARs (peroxisome proliferator-activated receptors) are ligand-activated nuclear transcription factors that serve as master regulators of metabolic homeostasis, governing lipid oxidation, glucose metabolism, inflammatory signaling, and fibrogenic activity.
Lanifibranor is an investigational next-generation pan-PPAR agonist with a differentiated, balanced activation profile across all three PPAR isoforms α, δ, γ — intended to achieve meaningful receptor engagement without the tolerability limitations associated with selective or partial PPAR agonism.
PPAR-α
Reduces hepatic fat accumulation, promotes fatty acid oxidation, and attenuates inflammatory signaling.
PPARδ
Modulates innate immune responses, promotes anti-inflammatory activity, and suppresses hepatic stellate cell activation.
PPAR-γ
Restores insulin sensitivity, induces adiponectin production, and inhibits fibrogenic signaling in the liver.
Through simultaneous, balanced engagement of all three isoforms, the pan-PPAR approach aim to address the underlying pathophysiology of the disease as well as provide a direct anti-fibrotic effect, thereby acting on two fronts simultaneously – targeting the metabolic dysfunction that drives MASH progression, while also targeting fibrogenesis directly through the mechanism itself.
This mechanistic rationale is supported by preliminary clinical evidence and reflects a scientifically grounded approach to a disease that demands more than a single-organ solution.
Our Clinical Program
Our product candidate, lanifibranor is an investigational, first-in-class pan-PPAR agonist being evaluated for the treatment of MASH, with the potential to address multiple disease pathways—including liver fat, inflammation, and fibrosis—while targeting systemic metabolic drivers, in a once-daily oral therapy.
The Phase 2b NATIVE study evaluating lanifibranor in patients with biopsy-confirmed, noncirrhotic MASH was completed in 2020. Lanifibranor was the first drug in development to simultaneously achieve MASH resolution without worsening of fibrosis and Fibrosis improvement without worsening as well as the dual endpoints of MASH resolution and Fibrosis improvement in a Phase 2b study. The positive results established a compelling foundation for the ongoing Phase 3 program, the NATiV3 study.
Key Clinical Highlights (1200mg Dose)
MASH resolution
49
of patients saw their MASH resolve without their scarring getting worse (vs. 22% for placebo).
Fibrosis improvement
48
of patients saw at least a one-stage improvement in liver scarring without their MASH getting worse (vs. 29% for placebo).
Dual benefit
35
of patients achieved both MASH resolution and fibrosis improvement simultaneously (vs. 9% for placebo).
Beyond the liver
Lanifibranor also showed significant improvements in overall cardiometabolic health, including better blood sugar control (HbA1c), improved insulin sensitivity, and healthier cholesterol levels.
Safety
Lanifibranor was well-tolerated.
Phase 3 NATiV3 Trial
We are currently conducting NATiV3, a global Phase 3 study to evaluate the long-term safety and effectiveness of lanifibranor.
Participants in our NATiV3 trial are adults with biopsy-confirmed MASH and moderate-to-advanced scarring (F2–F3). The trial’s is designed as a pivotal trial intended to support applications for FDA approval in the U.S. and marketing authorization from the European Commission in the E.U.
Topline results are anticipated in the last quarter of 2026.
